Diabetes and the hypoglycemic syndrome
The different mechanisms of action of the various classes of hypoglycemic drugs makes combined therapy feasible the sulfonylureas and meglitinides stimulate insulin production by different mechanisms, the biguanides reduce glucose production by the liver and excretion from the Patients with type 2 diabetes, with unsatisfactory control after taking metformin for 6 months, were randomized to metformin alone, repaglinide alone, or metfor-min + repaglinide (each 27 patients) (30). Combined therapy reduced HbA1c after 3 months by 1.4 and fasting glucose by 2.2 mmol l. Repaglinide alone or in combination with metformin increased insulin concentrations. The most common adverse effects were hypoglycemia, diarrhea, and headache. Gastrointestinal adverse effects were common in those taking metformin alone and body weight increased in both groups taking repaglinide. In a prospective, randomized, double-blind, placebo-controlled study for 24 weeks, 701 patients took nategli-nide 120 mg before the...
Drugs used for lowering the glucose level in the blood are called hypoglycemic agents. Likewise, substances that raise the level of glucose in the blood are called hyperglycemic agents. Changes in the level of glucose in the blood can be caused by various reasons, the primary cause being diabetes mellitus. Diabetes mellitus is a metabolic disease associated with a high level of blood sugar and as a rule, disturbance of carbohydrate, lipid, and protein metabolism. The most common biochemical condition in diabetes mellitus is ketoacidosis. Insulin and other hypoglycemic agents are used to treat diabetes mellitus. Depending on the condition of the organism, diabetes is classified into two types. Insulindependant (type I), in which there is suppression of endogenous insulin production by the organism itself, and insulin-independent (type II), which results either because of insufficient insulin production, or because of a breakdown of insulin receptors, which is usually a result of other...
A retrospective analysis of a pharmacy database of over 60 million Americans has shown that many do not persist in taking particular oral hypoglycemic drugs (51C). Of 11.6 million patients identified as continuously benefit-eligible for mail and retail prescriptions, 136 466 had received a first prescription for an oral hypo-glycemic drug between 1 October 1997 and 31 March 1999. The 12-month persistence rate ranged from 31 for a-glucosidase inhibitors to 60 for metformin. Compliance rates were 70-80 , and 36 of the patients who continued to use oral drugs changed treatment one or more times. The number of changes increased with increased follow-up, and more than half of the patients had at least one change in therapy. LDL cholesterol increased with acarbose (54C). Acarbose caused flatulence in 30 and diarrhea in 3 and gliclazide caused at least one mild attack of hypoglycemia in 10 .
Hypoglycemia, producing loss of consciousness in some cases, can occur in non-diabetic individuals who are taking beta-adrenoceptor antagonists, particularly those who undergo prolonged fasting (178) or severe exercise (179,180). Patients on maintenance dialysis are also at risk (181). It has been suggested that non-selective drugs are most likely to produce hypoglycemia and that cardio-selective drugs are to be preferred in at-risk patients (182), but the same effect has been reported with atenolol under similar circumstances (180). Two children in whom propranolol was used to treat attention deficit disorders and anxiety became unarous-able, with low heart rates and respiratory rates, due to hypoglycemia (183). Hypoglycemia can be caused by reduced glucose intake (fasting), increased utilization (hyperinsulinemia), or reduced production (enzymatic defects). One or more of these mechanisms can be responsible for hypoglycemia secondary to drugs. Children treated with propranolol may...
Diagnosis of hypoglycemia It is easy to read glucose meters wrongly (SEDA-25, 508). Hy-poglycemia was missed when a patient inadvertently switched the glucose meter from mmol l to mg dl and read 266 mg dl as 26.6 mmol l and 158 mg dl as 15.8 mmol l (1A). Three diabetic patients on chronic ambulatory peritoneal dialysis (CAPD) had symptoms of hypoglycemia when glucose readings on strips were higher than 4 mmol l (2c). Venous testing showed glucose concentrations as low as 1.8 mmol l. Large amounts of glucose are used in CAPD, which not only affects the regulation of diabetes but can also affect the peritoneal wall. Since 1999 icodextrin has been used in dialysis fluids. Icodextrin is glucose free and reduces the need for insulin. However, it is also absorbed systematically and can be metabolized to maltose and maltotriose. Paper systems that use either glucose oxidase or glucose dehydrogenase overestimate glucose readings when icodextrin is used, and patients and their carers are not...
They slow down food digestion in the gut, reducing peak blood glucose concentrations after meals. They also prevent reactive hypoglycemia, as can be seen after gastric operations, in dumping syndrome, and in idiopathic forms. When carbohydrates appear in the colon, bacterial fermentation can occur, leading to gastrointestinal adverse effects, of which flatulence and loose stools are the most frequent. During long-term treatment the colonic bacterial mass can increase. In elderly patients acarbose increases insulin sensitivity but not insulin release (1). Acarbose may reduce the incidence of colon cancer, the risk of which is 30 higher in people with diabetes than in the non-diabetic population (2).
In an open study in 57 patients acarbose and gliclazide had the same effects on HbA1c, blood glucose, and lipids, but the ratio of HDL to LDL cholesterol increased with acarbose (14). Acarbose caused flatulence in 30 and diarrhea in 3 and gliclazide caused at least one mild attack of hypoglycemia in 10 .
More than half of the patients receiving this drug by the parenteral route experience some adverse reaction. Severe and sometimes life-threatening reactions include leukopenia (low white blood cell count), hypoglycemia (low blood sugar), thrombocytopenia (low platelet count), and hypotension (low blood pressure). Moderate or less severe reactions include changes in some laboratory tests, such as the serum creatinine and liver function tests. Other adverse reactions include anxiety, headache, hypotension, chills, nausea, and anorexia. Aerosol administration may result in fatigue, a metallic taste in the mouth, shortness of breath, and anorexia.
Rifampin is contraindicated in patients with a history of hypersensitivity to the drug. The drug is used with caution during lactation, in patients with hepatic and renal impairment, and during pregnancy. Serum concentrations of digoxin may be decreased by rifampin. Isoniazid and rifampin administered concurrently may result in a higher risk of hepatotoxicity than when either drug is used alone. The use of rifampin with the oral anticoagulants or oral hypoglycemics may decrease the effects of the anticoagulant or hypoglycemic drug. There is a decrease in the effect of the oral contraceptives, chloram-phenicol, phenytoin, and verapamil when these agents are administered concurrently with rifampin.
Two deletions of the p85a regulatory subunit have been reported. A deletion of the first exon of p85a interrupts the expression of the full-length protein but does not affect the p55a and p50a splice variants (39). These animals develop a B-cell immunodeficiency and, surprisingly, increased insulin sensitivity and hypoglycemia. Deletion of all splice variants of p85a and leads to death of most of the animals within 4 d (40). Interpretation of this phenotype is hampered owing to upregulation of p85P and a reduction in the levels of p110a and p110P, supporting a role for p85a in protecting the catalytic subunits from proteolysis. P85P deletion also results in mice with improved insulin sensitivity and hypoglycemia (41).
Biological Causes of Anxiety It is important to rule out any medical causes of anxiety. Thyroid disorders, hypoglycemia, Cushing's disease, and pheochromocy-toma, a rare tumor of the adrenal gland, can cause symptoms similar to anxiety. You should consider a medical exam if your anxiety does not have an obvious cause.
The features appear to be arterial hypotension, brady-cardia due to sinus node depression and atrioventricular block, and congestive cardiac failure and angina (147-149). Although the therapeutic effects are different according to the drug, in overdosage the effects are similar (145). Severe metabolic acidosis (usually lactic acidosis) and generalized convulsions can also occur (150) and hypoglycemia has been reported (151). Non-cardiogenic pulmonary edema has been reported with diltiazem (152) and verapamil (153). Several deaths have occurred with verapamil.
Insulin therapy continues to be the cornerstone of treatment in T1DM, but is underutilized in the treatment of T2DM. Some investigators believe that multiple daily injections of insulin are disliked by patients and are partly responsible for patients not reaching goal (15,16). This demonstrated resistance to the implementation or administration of insulin therapy has been well documented. Often the reasons cited by clinicians to delay insulin therapy include fear of patient loss from practice, lack of time to implement, and clinical inertia, or the wait and see approach. Patient's reasons for delaying insulin therapy include the frequent asymptomatic course of diabetes, patient refusal to follow directions, and importantly, injections and hypoglycemia (15,16,693). Thus, inhaled insulin may help to overcome some of these concerns.
But these reports generally do not mention the metabolic values in the neonate. There has been one report of chronic fetal bradycardia associated with a low serum potassium in the diuretic-treated mother (152). Infusion of potassium restored maternal electrolytes and fetal heart rate. Normal delivery followed later, and electrolyte values in the child were normal. With regard to glucose handling, Senior and others (153) have raised the possibility that thiazide treatment of the mother can lead to neonatal hypoglycemia. In the absence of other predisposing factors, thiazides had been given to the mothers of 57 of their affected children, and, in the general population, the risk of neonatal hyperglycaemia was increased five-fold by thiazide treatment of the mother.
More recent studies have also highlighted the risks of severe disease and death in pregnant women. In an area of Thailand with low malaria transmission, the risk of severe malaria is threefold greater in pregnant versus nonpregnant women (Luxemburger et al. 1997), but mortality is prevented by early detection and prompt treatment (Nosten and McGready 2003). In Gujarat, India, fatal complications of pregnancy malaria included cerebral malaria, post-partum hemorrhage, acute pulmonary edema, and hypoglycemia (Maitra et al. 1993).
In a double-blind, randomized, crossover study in 10 healthy subjects, subcutaneous glucagon-like peptide-1 after a 16-hour fast caused a near five-fold rise in plasma insulin concentration and circulating plasma glucose concentrations fell below the reference range in all subjects (6). One subject had symptoms of hypoglycemia. A rise in pulse rate correlated with the fall in plasma glucose concentration and there was an increase in blood pressure.
Intravenous quinine is the mainstay of therapy for severe or complicated malaria in pregnant women (Looareesuwan et al. 1985). Traditionally, CQ was the mainstay of therapy for uncomplicated malaria in pregnant women. In areas ofCQ resistance, SP or amodiaquine are recommended for nonpregnant individuals (Keuter et al. 1990 Winstanley 2003), but amodiaquine is not recommended in pregnant women due to a lack of safety data (Taylor and White 2004). In areas with chloroquine and SP resistance, artesunate combinations (McGready et al. 2003) or oral quinine in combination with clindamycin (Mc-Gready et al. 2001b) have been shown to be effective for outpatient treatment of pregnant women. Quinine is generally well tolerated, although hypoglycemia is a potentially fatal side effect (Kochar et al. 1995 McGready et al. 2001b), and has been reported after oral administration (Taylor and White 2004).
The nurse must assess the patient for signs and symptoms of hypoglycemia and hyperglycemia (see Table 49-1) throughout insulin therapy. The patient is particularly prone to hypoglycemic reactions at the time of peak insulin action (see the Summary Drug Table Insulin Preparations) or when the patient has not eaten for some time or has skipped a meal. In acute care settings, frequent blood glucose monitoring is routinely done to help detect abnormalities of blood glucose. Testing usually occurs before meals and at bedtime (see section on Managing Hypoglycemia ).
Anorexia, nausea, vomiting, epigastric pain, heartburn, diarrhea, hypoglycemia, allergic skin reactions Hyperglycemia, hypoglycemia, nausea, diarrhea, upper respiratory tract infection, sinusitis, headache, arthralgia, back pain Headache, pain, diarrhea, hypoglycemia, hyperglycemia, fatigue, infections Hypoglycemia due to hyperinsulinism Hypoglycemia
The thiazolidinediones, piogli-tazone and rosiglitazone, are given with or without meals. If the dose is missed at the usual meal, the drug is taken at the next meal. If the dose is missed on one day, do not double the dose the following day. If the drug is taken, do not delay the meal. Delay of a meal for as little as lh hour can cause hypoglycemia.
The American Diabetes Association has published revised guidelines on insulin administration, including storage of insulin, use and reuse of needles, alternatives to syringes, injection techniques, and patient management related to dosing of insulin, self-monitoring, and hypoglycemia (143). Developments in the administration of insulin through the skin, the mouth, the nose, and the lung have been reviewed (144). Methods of absorption other than subcutaneous, such as nasal insulin, buccal insulin, rectal insulin, and insulin in enteric-coated capsules, are still experimental. A problem in nasal administration is still how to get a daily reproducible dose (145). The frequency of hypoglycemia is comparable to the frequency with subcutaneous insulin (146). Nasal irritation, sometimes with congestion, and dyspnea (147) can occur. Pulmonary insulin, delivered by aerosol inhalation, is another experimental method. No lung obstruction was reported, but the uptake varied considerably (148)....
Three diabetic patients on chronic ambulatory peritoneal dialysis (CAPD) had symptoms of hypoglycemia when glucose readings on strips were higher than 4 mmol l (223). Venous testing showed glucose concentrations as low as 1.8 mmol l. Large amounts of glucose are used in CAPD, which not only affects the regulation of diabetes but can also affect the peritoneal wall. Since 1999, icodex-trin has been used in dialysis fluids. Icodextrin is glucose-free and reduces the need for insulin. However, it is also absorbed systematically and can be metabolized to maltose and maltotriose. Paper systems that use either glucose oxidase or glucose dehydrogenase overestimate glucose readings when icodextrin is used, and patients and their carers are not able to measure low blood glucose concentrations. Another factor is that during end-stage renal insufficiency, insulin catabolism is reduced. This contributes to the problems when CAPD is changed to automated (overnight) peritoneal dialysis, in which...
Problems with the use of blood glucose measurement systems are reported from time to time. For example, it is easy to read glucose meters wrongly (SEDA-25, 508). Hypoglycemia was missed when a patient inadvertently switched the glucose meter from mmol l to mg dl and read 266 mg dl as 26.6 mmol l and 158 mg dl as 15.8 mmol l (226).
During Ramadan, insulin lispro reduced the number of attacks of hypoglycemia and reduced postprandial blood glucose (4). It also reduced post-snack raised blood glucose concentrations when sugar-rich snacks were used (5). The combinations insulin lispro + insulin glargine and regular + NPH have been compared in a randomized, crossover study for 32 weeks in 25 patients (6). HbA1c was not different, but the total insulin dose was lower with insulin lispro + insulin glargine and there were fewer episodes of nocturnal hypoglycemia. episodes of hypoglycemia. When Mix25TM (25 insulin lispro plus 75 protamine lispro) was compared with 30 70 human insulin in an open, randomized, crossover study during Ramadan, the daily average blood glucose concentration was better with the insulin lispro combination. The number of hypoglycemic episodes was the same with the two formulations (8). In an open, randomized, single-dose, three-way, crossover trial, biphasic insulin aspart 30 (30 aspart plus 70...
When the androgens are administered to a patient with diabetes, blood glucose measurements should be done frequently because glucose tolerance may be altered. Adjustments may need to be made in insulin dosage, oral antidiabetic drugs, or diet. The nurse monitors the patient for signs for hypoglycemia and hyper-glycemia (see Chap. 49).
Adverse effects due to drug-drug interactions are not expected in diabetic patients using insulin and oral hypo-glycemic drugs that are not metabolized by CYP3A4 (for example tolbutamide, gliclazide, glibenclamide, glipizide, and metformin). The pharmacokinetic and safety data from clinical trials and postmarketing surveillance have been reviewed to assess the safety of itraconazole in diabetic patients with onychomycosis or dermatomycosis (54). Postmarketing surveillance, including all adverse event reports in patients taking itraconazole concomi-tantly with insulin or an oral hypoglycemic drug, revealed 15 reports suggestive of hyperglycemia and nine reports suggestive of hypoglycemia. In most patients there was no change in antidiabetic effect. From clinical trials in 189 diabetic patients taking itraconazole for various infections, one itraconazole-related adverse event was recorded this was a case of aggravated diabetes in a renal transplant patient who was also taking...
The p-adrenergic blocking drugs are contraindicated in patients with bronchial asthma, obstructive pulmonary disease, sinus bradycardia, heart block, cardiac failure, or cardiogenic shock and in patients with hypersensitivity to the drug or any components of the drug. These drugs are Pregnancy Category C and are used cautiously during pregnancy and lactation and in patients with cardiovascular disease, diabetes (may mask the symptoms of hypoglycemia), and hyperthyroidism (may mask symptoms of hyperthyroidism). The patient taking p-adrener-gic blocking drugs for ophthalmic reasons may experience increased or additive effects when the drugs are administered with the oral beta blockers. Co-administration of timolol maleate and calcium antagonists may cause hypotension, left ventricular failure, and condition disturbances within the heart. There is a potential additive hypotensive effect when the beta-blocking ophthalmic drugs are administered with the phenothiazines.
The most frequent adverse effect of meglitinides is hypo-glycemia. The overall incidence of hypoglycemia with repaglinide is similar to that reported with sulfonylureas, but the incidence of serious hypoglycemia is lower. Other adverse effects are respiratory tract infections and headache. Cardiovascular events and cardiovascular mortality are not different from those in users of sulfonylureas. In Europe, repaglinide is contraindicated in patients with severe liver dysfunction and it is not recommended in people over 75 years old in America the advice is to use repaglinide cautiously in patients with impaired liver function and there is no restriction on its use in elderly patients. In renal impairment, the half-life of repaglinide is prolonged. Reasons for withdrawal are hyperglycemia, hypoglycemia, and myocardial infarction (38).
Widespread use of NSAIDs, particularly in the elderly, who often take other drugs at the same time, leads to a high risk of clinically significant drug interactions, both pharma-cokinetic and pharmacodynamic. The inhibitory effects of azapropazone, oxyphenbutazone, and phenylbutazone on the metabolism of other drugs, such as oral anticoagulants, oral hypoglycemic drugs, and phenytoin, is an example of a pharmacokinetic mechanism. Other NSAIDs inhibit the renal excretion of lithium (although toxicity is less likely with aspirin, ibuprofen, and sulindac) and methotrexate. Pharmacodynamic mechanisms are exemplified by the interactions between indometacin and other NSAIDs (except perhaps sulindac) and with antihypertensive agents (including beta-blockers, diuretics, and ACE inhibitors). Interactions of NSAIDs with other drugs (230) are summarized in Tables 2 and 3.
The American Diabetes Association has published revised guidelines on insulin administration, including storage of insulin, use and reuse of needles, alternatives to syringes, injection techniques, and patient management related to dosing of insulin, self-monitoring, and hypo-glycemia (34S).
Adverse reactions associated with the administration of the thiazolidinediones include aggravated diabetes mel-litus, upper respiratory infections, sinusitis, headache, pharyngitis, myalgia, diarrhea, and back pain. When used alone, rosiglitazone and pioglitazone rarely cause hypoglycemia. However, patients receiving these drugs in combination with insulin or other oral hypo-glycemics (eg, the sulfonylureas) are at greater risk for hypoglycemia. A reduction in the dosage of insulin or the sulfonylurea may be required to prevent episodes of hypoglycemia.
Although elderly patients taking the oral antidiabetic drugs are particularly susceptible to hypoglycemic reactions, these reactions may be difficult to detect in the elderly. The nurse notifies the health care provider if blood sugar levels are elevated (consistently 200 mg dL) or if ketones are present in the urine.
In 70 non-insulin-dependent patients with diabetes, taking one of five different oral hypoglycemic drugs, 21 of prescriptions were associated with a low plasma sodium concentration, but it was lower than 129 mmol l in only 8 (62). Every oral hypoglycemic agent was associated with a low plasma sodium concentration, which normalized on withdrawal. Extreme hyponatremia was only seen with chlorpropamide and, in one case, with glibenclamide.
Gliclazide is available in various formulations with different kinetics in vivo and in vitro (127). Gliclazide MR is a modified-release formulation that allows once-a-day dosing. In a double-blind study 800 patients were randomized to gliclazide or gliclazide MR there were no differences in adverse reactions or hypoglycemia (128). When comparing identical doses of Diamicron and Diabrezide in an open, crossover study, Diabrezide had a larger acute and mid-term hypoglycemic effect than Diamicron (129). In a small study, gliclazide MR 30-120 mg day had similar efficacy to 80-320 mg day of the immediate-release formulation. The most commonly observed adverse events were arthralgia, arthritis, back pain, and bronchitis, which may not all have been directly related to the drug, as they also occurred with placebo. There was symptomatic hypoglycemia in about 5 . Glipizide GITS was also studied in 19 patients with type 2 diabetes in an open, randomized, two-way, crossover study for 5 days,...
In a parallel-group, double-blind, placebo-controlled, dose-ranging study of rosiglitazone 4, 8, and 12 mg day in 369 patients for 8 weeks after a run-in period, hemato-crit and hemoglobin, C peptide, fasting blood glucose, and fructosamine all fell (28). Hepatotoxicity, significant cardiac events, or hypoglycemia were not different from placebo. In 574 patients taking a sulfonylurea, twice-daily placebo (n 192 patients) was compared with rosiglitazone 1 mg day (n 199 patients) or rosiglitazone 2 mg day (n 183 patients) for 26 weeks (29). Rosiglitazone improved HbA1c. With the higher dose of rosiglitazone there were more cases of hypoglycemia and a small increase in mean body weight some patients complained of headache and upper respiratory tract infections. In 561 patients with HbA1c concentrations of at least 8.0 on stable treatment with a sulfonylurea, pioglita-zone was added for 16 weeks in a double-blind study (33). The incidence of edema increased from 2 in the placebo group to...
There is an increased risk for bone marrow suppression when levamisole or hydroxyurea are administered with other antineoplastic drugs. Use of levamisole with phenytoin increases the risk of phenytoin toxicity. Pegaspargase may alter drug response of the anticoagulants. When procarbazine is administered with other central nervous system (CNS) depressants, such as alcohol, antidepressants, antihistamines, opiates, or the sedatives, an additive CNS effect may be seen. Procarbazine may potentiate hypoglycemia when administered with insulin or oral antidiabetic drugs.
The adverse effects of disopyramide are mostly mediated by its effects on the cardiovascular system and by its anticholinergic effects. Disopyramide has a strong negative inotropic effect on the myocardium and can cause heart failure and hypotension. It prolongs the QT interval and can cause serious ventricular tachydysrhythmias. Anticholinergic effects can cause dry mouth, blurred vision, urinary retention, glaucoma, and erectile impotence. Hypoglycemia can also occur. Disopyramide can cause uterine contractions and should not be used during pregnancy. Angioedema has been reported rarely. Tumor-inducing effects have not been reported.
Some of the macrolide antibiotics have been reported to inhibit the clearance of disopyramide (SEDA-21, 200) (SEDA-22, 207), resulting in serious dysrhythmias or hypoglycemia. The mechanism of this interaction is presumed to be inhibition of dealkylation of disopyramide to its major metabolite, mono-N-dealkyldisopyramide. For example, in human liver microsomes the macrolide antibiotic troleandomycin significantly inhibited the mono-N-dealkylation of disopyramide enantiomers by inhibition of CYP3A4 (34). This interaction can result in serious dysrhythmias or other adverse effects of disopyramide. In a 59-year-old man taking disopyramide 50mg day the addition of clarithromycin 600 mg day caused hypo-glycemia, and the serum disopyramide concentration rose from 1.5 to 8.0 mg ml (37). The ratio of plasma insulin concentration to blood glucose concentration was greatly increased, suggesting that hypersecretion of insulin was responsible, confirming the likelihood that the hypoglycemia was...
Bnouham et al. 64 examined antidiabetic effect of an aqueous extract of the aerial parts of Urtica dioica (nettle), a plant used in eastern Morocco for both diabetes and hypertension, on hyperglycemia induced by oral glucose tolerance test (OGTT) and on alloxan-induced diabetic rats. The authors showed a strong antihyperglyce-mic effect of the plant (250 mg kg-1) during the first hour after glucose loading in rats under OGTT (33 versus control) but a lack of hypoglycemic effect in alloxan-induced diabetic rats. Furthermore, intestinal glucose absorption was significantly reduced in situ in jejunum segment, which suggests that the extract may act on glucose homeostasis via an extrapancreatic mechanism. Another medicinal plant, Globularia alypum (Globulariacee), known locally as ain larnab, which is frequently used to cure diabetes in eastern and southern Morocco 63, 67 and is also known to be laxative 3 , stomachic, a good purgative, and sudorific 5 , has been evaluated for its...
McAulay V, Deary IJ, Ferguson SC, Frier BM. Acute hypoglycemia in humans causes attentional dysfunction while nonverbal intelligence is preserved. Diabetes Care 2001 24 1745-50. 14. Miller CD, Philips LS, Ziemer DC, Gallina DL, Cook CB, El-Kebbi IM. Hypoglycemia in patients with type 2 diabetes mellitus. Arch Int Med 2001 61 1653-9. 15. Charlton R, Smith G, Day A. Munchausen's syndrome manifesting as factitious hypoglycemia. Diabetologia 2001 44 784-5. 22. Evers IM, Ter Braak EWMT, De Valk HW. Van der Schoot W, Jansen N, Visser GHA. Risk indicators predictive for severe hypoglycemia during the first trimester of type 1 diabetic pregnancy. Diabetes Care 2002 25 554-9. 23. Danne T, Mortensen HB, Hougaard P, for The Hvidore Study Group. Persistent differences among centers over 3 years in glycemic control and hypo-glycemia in a study of 3805 children and adolescents with type 1 diabetes. Diabetes Care 2001 24 1342-7. 51. Boccuzzi SJ, Wogen J, Fox J, Sung JCY, Shah AB, Kim J....
Although a significant teratogenic risk is not expected with A-blockcrs, there is a theoretical risk of neonatal i-receptor blockade -leading to neonatal bradycardia, hypotension, and hypoglycemia (Rubin 1983A. Dumez 1981). Respiratory distress and apnea have been reported following in utero exposure to propranolol until birth, but such adverse effects are rare (Tumstall 1969). There are conflicting opinions regarding the safety ol stopping medication with ,1-blockers 24-48 hours before delivery. Neonatal symptoms of i-blockade are usually mild and improve within 48 hours of delivery with no long-term effects. Nevertheless, obstetricians, midwives, and pediatricians should be informed about maternal medication and made aware of the possibility of neonatal toxicity. Recommendation, -receptor blockers such as labetalol, propranolol, and metoprolol, which have been in long-term use, are among the first-line drugs of choice for treating hypertension in pregnancy. Treatment with other...
Better than does regular human insulin because it more closely mimics the body's natural insulin. It also lowers the risk of low blood sugar reactions from midnight to 6 AM in patients with type l diabetes. The longer acting insulins are given before breakfast or at bedtime (depending on the health care provider's instructions). Many patients are maintained on a single dose of intermediate-acting insulin administered SC in the morning.
The carbonic anhydrase inhibitors brinzolamide, dorzolamide, and for systemic application, acetazolamide, which are used for glaucoma therapy, have not been systematically studied. A new bom of 34 weeks' gestation was tachypnoic, and a combined respiratory-metabolic acidosis, hypoglycemia, and hypokalemia was diagnosed. Its mother had been treated with 750 mg azetazolamide daily during the 3 days prior to delivery. There was 2.9pg ml in the blood of the newborn when this was measured 5 hours after birth - almost a therapeutic concentration (3-10(ig ml). There was no substance detectable on day 11. Further development of the child was uneventful (Ozawa 2001). There were no birth defects or postnatal disorders observed in the newborn of 12 women using, on average, 500 mg azetazolamide daily for idiopathic increased intracranial pressure. Nine of them were exposed during the first trimester (Lee 2005).
Insulin plus metformin (27 patients, 2000 mg day) or troglitazone (30 patients, 600 mg day) in patients with type 2 diabetes using at least 30 U day was compared with insulin alone (30 patients) for 4 months (42). Body weight increased in the insulin and the insulin plus trogli-tazone groups. In the insulin plus metformin group there were significantly more gastrointestinal adverse effects but less hypoglycemia than the other groups.
Hypoglycemic drugs Reduction in hypotensive effect, probably related to impaired prostaglandin synthesis (causing salt and water retention) and vascular prostaglandin synthesis (causing vasoconstriction) Reduction in natriuretic and diuretic effects can exacerbate congestive cardiac failure Gastrointestinal tract mucosal damage inhibition of platelet aggregation increased risk of gastrointestinal bleeding in patients taking anticoagulants Potentiation of hypoglycemic effects (mechanism unknown)
Metabolism Hypoglycemia associated with co-trimoxazole may be due to hyperinsuline-mia, sulfamethoxazole being structurally similar to the sulfonylureas. Hypoglycemia is more common in elderly people and in those with renal impairment. Two cases of co-trimoxazole-induced hypoglycemia have been reported in men with HIV infection (42A, 43A). The high insulin and C peptide concentrations in this case are consistent with hyperinsuline-mic hypoglycemia due to co-trimoxazole. Fluconazole and sulfamethoxazole both inhibit CYP2C9, which metabolizes gliclazide. Co-administration of these three drugs resulted in severe hypoglycemia. This adverse event may become more common as more HIVpositive patients taking protease inhibitors develop diabetes requiring sulfonylurea therapy.
Potentiation or prolongation of other drug effects due to inhibition of hepatic drug-metabolizing enzymes Alcohol (all types) Anesthetics Antihistamines Antiparkinsonian agents Barbiturates Benzodiazepines Chloral hydrate Hypoglycemic agents Opiate analgesics Thyroid extract Tricyclic antidepressants
Neonatal morbidity include macrosomia (an extremely large newborn) with immature organ functions or hypotrophy, and postpartum metabolic derangements of the newborn - especially hypoglycemia. Insulin action changes during the course of pregnancy. At 10-14 weeks' gestation, insulin sensitivity is slightly increased however, it then declines for the rest of the pregnancy, with insulin resistance being highest late in the third trimester. Insulin sensitivity rebounds with the delivery of the placenta. In cases of pre-existing diabetes, these changes contribute to a degree of hypoglycemia in the first trimester and increased insulin requirements during later pregnancy, and reinstitution of the pre-pregnancy insulin requirement after delivery.
Targets, in plasma, bound to a corticosteroid-binding globulin. Unbound or free corticosteroids enter the target-cells and bind to a cytoplasmic corticosteroid receptor. The dimer corticosteroid-receptor enters then the nucleus and binds to a DNA binding receptor and stimulates therefore the synthesis of specific proteins with physiological properties. A number of plant triterpenoids and steroids share with human steroid a cyclopentanoperhydrophenanthrene skeleton and are thereby able to interfere with the manifold physiological activities of steroidal hormones, hence exhibiting anti-inflammatory, diuretic, hypoglycaemic, estrogen antagonist, and abortifacient properties (Pakrashi A et al., 1977 Wadhwa V et al, 1986 Figs. 63-64). Normal and alloxan-induced diabetic rabbits fed with Achyranthes aspera L. or aqueous and methanolic extracts, develop a dose-dependent hypoglycaemia at doses of 2 g Kg, 3 g Kg, and4g Kg (AkhtarMS etal., 1991).The anti-inflammatory property of Achyranthes...
Beta-blockade reduces mortality in patients with heart failure by at least a third when initiated carefully, with gradual dose titration, in those with stable heart failure (34,35). Similarly, beta-blocker prescribing should be encouraged in people with diabetes, since they have a worse outcome after cardiac events and beta-blockade has an independent secondary protective effect (36,37). The small risk of masking metabolic and autonomic responses to hypoglycemia, which was only a problem with non-selective agents in type I diabetes, is a very small price worth paying in diabetics with coronary heart disease.
A varied diet of foods from different food groups, low on fats and sugars, eaten two to four times a day is sufficient if you do not have any other significant health problems. If you do, then it is important to alter your diet no matter what psychiatric problems you are experiencing. For example, people with diabetes need to minimize their sugar intake in order to avoid hypoglycemic reactions. People with high blood pressure and certain kinds of heart problems generally do better if they maintain diets that are low in salt.
The effect of age on the response to metformin has been studied in 174 patients aged over 70 years, not well-controlled on glibenclamide 7.5 mg day or gliclazide 120 mg day (80). They were given either maximal doses of a sulfonylurea (glibenclamide 15 mg day or gliclazide 240 mg day) or a sulfonylurea + metformin (1700 mg day). Renal function and liver function were normal. There were nine cases of non-severe hypoglycemia in the first group. In the second group there were two cases of hypoglycemia after delayed meals and 35 had transient mild gastrointestinal discomfort. There were no increases in lactic acid. Lipid
Adverse reactions in the fetus and the newborn (tremors, tachycardia, hypoglycemia, and hypokalemia) have been reported, especially when high doses of 32-agonists are used. The effects are less common when used by inhalation, and they are reversible. Raker and Flanagan reported a case of maternal and fetal tachycardia after inadvertanl inhalation of high doses of albuterol for 24 hours in week 33 (Baker 1997). The heart rale became normal after the discontinuation of albuterol.
Neither glibenclamide nor glipizide were detected in the breast-milk of three mothers. Hypoglycemia was not observed in any of the children. In another eight women receiving a single dosage of gliben clamide, no substance was found in milk. A high protein-binding of 98 could explain these results (Feig 2005). Only small amounts of metformin are found in mothers' milk the weight-adjusted dose for a fully breastfed child is 0.1-0.7 (Briggs 2005, Gardiner 2003, Hale 2002). Hypoglycemia was not reported in breastfed infants. Metformin concentrations in breast milk remained stable over the time of observation. Growth, motor-social development, and illness requiring a pediatrician's visit were assessed in 61 nursing infants (21 male, 40 female) and 50 formula-fed infants (19 male, 31 female) born to 92 mothers with polycystic ovary syndrome (PCOS) taking a median of 2.55 g metformin per day throughout pregnancy and lactation. At 3 and 6 months of age, the weight, height, and motor-social...
Hypoglycemia and raised serum concentrations of glibenclamide, which is metabolized by CYP2C9, occurred after treatment with ciprofloxacin for 1 week in a patient taking long-term glibenclamide (72). Hypoglycemia occurred in a patient treated with insulin and ciprofloxacin 500 mg bd (29).
Ammi majus is also known as bishop's weed or large bullwort, and Ammi visnaga as toothpick weed. They have numerous active ingredients, including ammirin, angenoma-lin, kellactone, majurin, and marmesin, furanocoumarins (psoralen, bergapten, isopimpinellin, imperatorin, umbelli-prenin, xanthotoxin), and flavonol triglycosides (kaemp-ferol, isorhamnetin). In modern times they have been used to treat vitiligo, since they contain psoralens, and have several different pharmacological effects in experimental animals, including hypoglycemic effects (3), antischisto-somal effects (4), and inhibition of nephrolithiasis (5).
Metabolic A San Francisco woman with a history of diabetes and high blood pressure was hospitalized in January 2001 with life-threatening hypoglycemia after she consumed Anso Comfort capsules. This may have been due to an interaction of chlordiazepoxide with other unspecified medications that she was taking.
When the drug is given IM or IV, the nurse prepares the drug according to the manufacturer's directions. When the drug is given by the IV route, it is important to infuse the drug over 1 hour. When the drug is given by aerosol, the nurse uses a special nebulizer (Respirgard II) and delivers the drug until the chamber is empty. It also is a good idea to explain or demonstrate the use of the nebulizer to the patient. The nurse monitors blood pressure frequently during administration because sudden, severe hypotension may occur after administration. Because hypotension can occur after a single dose, the nurse should always have the patient lying down when the drug is administered. The nurse assesses the patient for signs of hypoglycemia (weakness, diaphoresis, cool skin, shakiness) and hyperglycemia (flushed dry skin, fruity breath odor, increased thirst, and increased urination).
It is used as a sweetener in many sugar-free food products and confectioneries. Sorbitol-containing food products are often recommended for patients with diabetes, because sorbitol does not raise blood glucose concentrations or require insulin for its metabolism (12).
Drug interactions A San Francisco woman with a history of diabetes and high blood pressure was hospitalized in January 2001 with a life-threatening low blood sugar concentration after she consumed Anso Comfort capsules (7a). The hospitalization may have been necessitated by a drug interaction of chlordiazepox-ide and the prescribed medications for her other medical conditions.
Cardioselective drugs are less likely to produce adverse effects in patients with type I diabetes than non-selective drugs. At present, hypoglycemia in patients with type I diabetes mellitus is the only clinical problem in which cardioselectivity is considered important. Even there, any potential advantages of cardioselective drugs in minimizing adverse effects apply only at low dosages, since cardioselectivity is dose-dependent.
Some common activities, such as mental effort (347), cigarette smoking, and coffee drinking (348,349), can produce stress associated with increased catecholamine secretion. In the presence of a non-selective beta-adreno-ceptor antagonist, there can be a marked diastolic pressor response, due to mechanisms identical to those described above in hypoglycemia in diabetes. This effect may be smaller with cardioselective drugs.
Metformin was given as an adjunct to insulin in a double-blind, placebo-controlled study in 28 adolescents needing more than 1 U kg day (19). The dose of metformin was 1000mg day when body weight was under 50 kg, 1500 mg day when it was 50-75 kg, and 2000 mg day when it was over 75 kg. Metformin lowered insulin requirements. The number of episodes of hypoglycemia increased compared with placebo. There was gastrointestinal discomfort in six patients taking metformin and five taking placebo. A comparable placebo-controlled study was reported in 353 patients with type 2 diabetes for 48 weeks. All were taking insulin, and HbA1c fell in those who also took metformin. Body weight was reduced by 0.4 kg by metformin and increased by 1.2 kg by placebo. Symptomatic episodes of hypoglycemia were more common with met-formin. There were mild transient gastrointestinal complaints in 56 and 13 respectively (20). Insulin plus metformin (27 patients, 2000 mg day) or troglitazone (30 patients, 600 mg...
The combination of metformin with other drugs that can lower the blood glucose concentration can result in severe hypoglycemia. The combination of metformin, which itself does not cause hypoglycemia, with an ACE inhibitor, nitrofuran-toin, and an NSAID, which all have glucose-lowering effects, and poor food intake may have led to hypoglyce-mia in this case.
Effects Licorice has been used to treat depression, as well as digestive, respiratory, kidney, and bladder ailments. In Japan, it has been used to treat chronic hepatitis B and C. It can also inhibit tooth decay, inhibit the growth of cancer in vitro and in mice, is helpful in the treatment of sore throats and coughs, and may aid in the treatment of Addison's disease. An extract, glycyrrhizin, has been used to treat such viruses as herpes zoster (shingles), herpes simplex 1, polio type 1, and vaccinia in vitro, and to inhibit HIV. Derivatives have also led to such drugs as Carbenoxolone, used in the treatment of various types of ulcers. Used by herbalists to treat allergies, asthma, chronic fatigue, emphysema, fever, hypoglycemia, and inflammation of the bowels.
The onset of action with the AERx system is approximately 10 min with peak insulin concentrations occurring approximately 1 h after inhalation (30). Dose effects the duration of action with a dose of 0.3 units kg lasting 5h and a dose of 1.8 units kg lasting 8h (30). Pharmacokinetic studies found that inhaled delivery using the AERx system resulted in rapid absorption of insulin and a corresponding faster decline in plasma glucose compared with subcutaneous (SC) administration (Table 3) (29). Intrapatient variability is similar in T1DM patients given equivalent doses of either SC regular insulin or inhaled insulin (31). The speed of absorption and resultant hypoglycemic activity is dependent on the volume and depth of breath, hence the inhaler design (29).
It has been shown to be effective in reducing A1C levels in T1DM and T2DM. As with other insulin, a risk of hypoglycemia is present, and Exubera has similar rates of hypoglycemia as SC regular insulin. Safety data is complete through 2 years with Exubera, and small changes in FEV1 and DLco have been observed, but are reversible upon discontinuation. Other inhalation systems such as AERx, AIR, and Technosphere are in development, and the area of alternative delivery of peptides continues to be an active area of research.
Hydrochlorothiazide, chlorthalidone, mefruside, bemetizide, ben-dwflumethiazide, butizide, chlorazanil, clopamide, indapamide, metolazone, polythiazide, quinethazone, trichlormethiazide, and xipamide are benzthiazide derivatives whose action depends on the inhibition of absorption of sodium and chloride in the distal tubule area. These drugs cause a potassium loss and lead to a reduction in the plasma volume In addition, they inhibit the excretion of uric acid. Benzthiazides are well-absorbed in the intestinal tract and are excreted unchanged in the urine. They cross the placenta and, when they are given sub partu, can lead to electrolyte changes (hyponatremia, hypokalemia), to thrombopenia, and to reactive hypoglycemia in the newborn as a result of their diabetogenic effect on the mother. In addition, prolonged labor has been described as a result of the inhibitory action on the smooth muscles.
Diuretics are no longer part of the standard therapy for hypertension and edema during pregnancy they should only be used for particular indications. In such cases, hydrochlorothiazide is the diuretic of choice. Furosemide can also be given when treatment of heart or renal failure requires a diuretic. When therapy is long term, the mother's electrolytes and hematocrit should be monitored and the development of oligohydramnios ruled out. If treatment is continued throughout the pregnancy, hypoglycemia in the newborn should be determined. Mannitol may be used during pregnancy when an osmotic diuretic is necessary. Other benzthiazide derivatives, ethacrynic acid, amiloride, triamterene, and aldosterone antagonists should be avoided during pregnancy. If therapy with aldosterone antagonists is absolutely necessary, spironolactone should be chosen. None of the diuretics is an indication for interrupting the pregnancy.
There is an increased risk for hypoglycemia when products containing sulfamethoxazole are administered with oral antidiabetic drugs such as tolbutamide, tolazamide, and glipizide and an increased risk of hemorrhage when given with oral anticoagulants. An increased urinary pH decreases the effectiveness of methenamine. Therefore, to avoid raising the urine pH when taking methenamine, the patient should not use antacids containing sodium bicarbonate or sodium carbonate. Nalidixic acid may increase the effects of the anticoagulants.
Hypoglycemic, an effect that has been attributed to isoorientin, which is present in several species of Gentiana (1) and which also has antinociceptive and anti-inflammatory effects in animals (2). Some species of Gentiana inhibit monoamine oxidase (3) and acetylcholinesterase (4) in vitro.
The endocrino part of the pancreas produces and secretes insulin, glucagons, and somatostatin. Insulin is necessary for storage of metabolic substrates such as glucose, fatty acids, and amino acids. Glucagon is important for the reverse regulation in hypoglycemia. There is less information on the use of insulin aspart during pregnancy. A multinational European study compared the maternal and fetal complications of type I diabetic pregnant women on regular insulin (Actrapid ) (n 165) and on insulin aspart (n 157). Similar numbers of live births, fetal losses, and congenital anomalies were reported in both groups, as well as similar rates of neonatal hypoglycemia and infant birth characteristics. Overall glycemic control was similar, as well as the maternal and obstetric complications during pregnancy (Hod 2006). The other insulin analogs, insulin glulisin, insulin detemir, and insulin glargine, have rarely been used in pregnancies to date. The long-acting insulin glargine might worsen...
Adverse reactions seen with the sulfonylureas include hypoglycemia, anorexia, nausea, vomiting, epigastric discomfort, weight gain, heartburn, and various vague neurologic symptoms, such as weakness and numbness of the extremities. Often, these can be eliminated by reducing the dosage or giving the drug in divided doses. If these reactions become severe, the health care provider may try another oral antidiabetic drug or discontinue the use of these drugs. If the drug therapy is discontinued, it may be necessary to control the diabetes with insulin.
Adverse reactions associated with the biguanide (met-formin) include gastrointestinal upsets (such as abdominal bloating, nausea, cramping, diarrhea) and metallic taste (usually self-limiting). These adverse reactions are self-limiting and can be reduced if the patients are started on a low dose with dosage increased slowly and if the drug is taken with meals. Hypoglycemia rarely occurs when metformin is used alone.
Theses drugs are contraindicated in patients with hypersensitivity to the drug, type I diabetes, and diabetic ketoacidosis. Both repaglinide and nateglinide are Pregnancy Category C drugs and are not recommended for use during pregnancy and lactation. These drugs are used cautiously in patients with renal or hepatic impairment. Certain drugs, such as NSAIDs, salicylates, MAOIs, and beta adrenergic blocking drugs, may potentiate the hypoglycemic action of the meglitinides. Drugs such as the thiazides, cortico-steroids, thyroid drugs, and sympathomimetics may decrease the hypoglycemic action of these drugs. The nurse must closely observe the patient receiving one or more of these drugs along with an oral antidiabetic drug.
Which of the following would the nurse mostly likely choose to terminate a hypoglycemic reaction D. the patient is at increased risk for hypoglycemia 5. In patients receiving oral hypoglycemic drugs, the nurse must be aware that hypoglycemic reactions D. may occur more frequently in patients receiving oral hypoglycemic drugs.
In 80 patients taking metformin 850 or 1000 mg tds plus NPH insulin at bedtime, metformin was withdrawn and repaglinide 4 mg tds added in half of the patients for 16 weeks (37). In the repaglinide group the dose of insulin increased slightly and weight gain was 1.8 kg more. Mild hypoglycemia occurred more often in the metformin group nightly episodes of hypoglycemia occurred only with repaglinide. One patient taking repaglinide had a myocardial infarction, and one had three separate hospitalizations for chest pain (myocardial infarction was excluded). No specific data were presented about gastrointestinal adverse effects or infections.
Precautions It should not be taken by anyone who is allergic to stimulants, has heart disease or irregular heartbeats, who suffers from insomnia, anxiety, or panic disorders, or has a peptic ulcer of the stomach or duodenum. A physician should be consulted first if any of the following conditions are present hypoglycemia, epilepsy, or high blood pressure. To discontinue use, gradually decrease the amount over a month or more, or headaches, irritability, and drowsiness may result. Other adverse effects include heart palpitations, high blood pressure, muscle twitches, rapid heartbeat, low blood sugar, nervousness, insomnia, increased urination, anxiety, indigestion, increased production of gastrointestinal acid, rectal itching, constipation, impaired concentration, a weakened immune system, bladder irritation and urinary problems (especially in women), and interference with DNA replication. It has been shown to trigger panic attacks in susceptible people which it does by lowering the...
It has been shown that prolonged treatment with glipizide in NIDDM patients significantly potentiated the action of circulating insulin and that this effect is most likely produced by an increased insulin receptor population. Reduction of serum glucagon levels with sulfonylurea administration suggests that its secretion is suppressed, thus contributing to the observed hypoglycemic effect. The result, then, is a physiologic outline of a mechanism. However, an exact mechanism at the molecular level is still elusive.
Circulatory symptoms and hypoglycemia have been cited from time to time in connection with the intake of i-S-rcceptor blockers via mother's milk. In contrast to the experience with subpartu administration, such an effect is not very probable. Nevertheless, acebutolol, atenolol, and sotalol should be viewed critically because the low protein binding and primarily renal excretion allow for the possibility
The new long-acting insulin analogue glargine insulin has been reviewed (26M ). In general one daily injection gives more constant insulin concentrations and fewer nightly attacks of hypoglycemia than NPH insulin. Treatment satisfaction appeared to be constantly better with glargine in 517 patients (27C). There was a consistent mean reduction in the perceived frequency of attacks of hypoglycemia. Other adverse effects were not mentioned. Glargine and NPH-insulin have been compared in 349 children and adolescents in a multicenter, open, randomized study (28C). Besides the usual thrice-daily regimen of regular insulin they used either glargine at bedtime or NPH at bedtime or twice daily. HbA1c did not differ. The target for fasting blood glucose was 4.4-8.8 mmol l, and 5 more patients who used glargine reached the target (44 compared with 39 of the patients who used NPH). Symptomatic hypoglycemia was similar with the two treatments. A 25-year-old woman and a 52-year-old woman injected...
A population pharmacokinetic study of intramuscular quinine (loading dose 20 mg kg salt diluted 1 1 in water) in 120 Ghanaian children with severe malaria showed predictable profiles, which were within the target range for quinine (15-20 mg ml) and independent of clinical and laboratory variables (1). Adverse events included skin induration or abscesses at the injection site (12 ), all of which resolved without surgical intervention, and hypo-glycemia (10 ), a special risk in children who were hypo-glycemic at presentation.
Nervous system Cerebral damage can occur after severe or repeated hypoglycemia. A 75-year-old man taking gliclazide 80 mg bd and metformin 850 mg tds became hypoglycemic and was treated successfully (83A). All hypo-glycemic drugs were withdrawn, but he received more through his doctor's prescription computer and again became hypoglycemic on two occasions. On the second he became unconscious for 4.5 hours and his plasma glucose was 1.2 mmol l. After resuscitation his abbreviated mental test was 5 10 and did not improve. He later became very aggressive and died of bronchopneumonia. Metabolism In an open comparative study in 57 patients acarbose and gliclazide had the same effects on HbA1c, blood glucose, and lipids, although the ratio of HDL LDL cholesterol increased during acarbose therapy (54C). Of those who took gliclazide 10 reported at least one mild hypoglycemic reaction. A 14-year-old non-diabetic girl took 15 tablets of gliclazide (1200 mg) and had gastric lavage 6 hours later....
In an 8-week non-interventional cohort study in 22 045 patients with type 2 diabetes, of whom 4.9 discontinued therapy, adverse advents occurred in 2.3 (85C). There were attacks of hypoglycemia in 0.3 . Of the 6547 patients taking glimepiride, 2.5 had adverse reactions and 0.4 had hypoglycemic reactions. In an open multicenter study 849 patients with poorly controlled diabetes were treated with glimepiride monotherapy for 6 months in doses that were titrated from 1 to 6 mg (86C). The authors tried to identify factors that could predict the response to glimepiride. Patients who achieved a fasting blood glucose below 7.7 mmol l and HbA1c below 7.5 or a reduction in fasting blood glucose of over 20 and or in HbA1c of at least 10 were defined as responders (57 of the 849 patients). Earlier treatment with other oral hypoglycemic drugs or long-standing diabetes increased the rate of non-responders. In 9.2 of the patients there were episodes of hypoglycemia, 1.4 per patient, and third-party...
Clinical and pharmaceutical aspects of rosigli-tazone have recently been reviewed (88M). Frequently reported adverse effects in many studies include weight gain, upper respiratory tract infection, injury, and headache for which no cause can be found. Fluid retention can lead to or exacerbate heart failure and pulmonary and general edema (see under Fluid balance). Hematocrit and hemoglobin are reduced. Changes in liver enzymes and bilirubin have not been reported, and although there have been some reports of hepatic-related adverse effect they have not been definitive (see also SEDA-25, 515). There are no drug interactions with other hypoglycemic agents.
Blighia sapida (akee) contains a large amount of a potent hypoglycemic amino acid, glycylglycylglycine, known as hypoglycin. Akee poisoning (Jamaican winter vomiting sickness or toxic hypoglycemic syndrome) is a potentially fatal illness. During an outbreak in 1991, symptoms included vomiting (77 ), coma (25 ), and seizures (24 ) (1). In 29 African children, all of whom died in 2-48 hours, there
The combination of alcohol and cocaine has been associated with fatal cardiac events and increased hepatoxicity. Alcohol in combination with an opiate or cannabis cause greater sedation and greater neurologic impairment than when used alone. Acute alcohol intoxication is associated with inhibition of hepatic enzymes and may increase blood levels of concurrent medication. Conversely, chronic alcohol use causes enzyme induction, leading to lower blood levels of antipsy-chotic drugs, antidepressants, valproic acid, carbamazepine, and some benzodiazepines. Griseofulvin, metronidazole, chlo-ramphenical and oral hypoglycemic agents may cause mild disulfiram-like reactions with alcohol. Alcohol and chloral hydrate compete for alcohol dehydrogenase concurrent ingestion leads to higher blood levels of both and increased intoxication (this combination is known as a 'Mickey Finn').
Deflazacort, an oxazoline derivative of prednisolone, was introduced as a potential substitute for conventional glucocorticoids in order to ameliorate glucose intolerance. In a randomized study in kidney transplant recipients with pre- or post-transplantation diabetes mellitus, 42 patients who switched from prednisone to deflazacort (in the ratio 5 6 mg) were prospectively compared with 40 patients who continued to take prednisone (SEDA-22, 445) (103). During the mean follow-up period of 13 months, neither graft dysfunction nor acute rejection developed in the conversion group, and there was improvement in blood glucose control. When the conversion group was stratified into those with pre- or post-transplantation diabetes, there were promising effects in the patients with posttransplantation diabetes. More than a 50 dosage reduction of hypoglycemic drugs was possible in 42 of those with post-transplantation diabetes. The risk of hyperglycemia requiring treatment in patients receiving...
Oral formulations of Momordica charantia (karela fruit, bitter melon) have hypoglycemic activity in non-insulin dependent diabetes mellitus (8,9), and can interfere with conventional treatment with diet and chlorpropamide (10). In 15 patients aged 52-65 years a soft extract of M. charantia plus half doses of metformin or glibenclamide or both in combination caused hypoglycemia greater than that caused by full doses during treatment for 7 days (11). Subcutaneous injection of a principle obtained from the fruit may lower blood glucose concentrations in juvenile diabetes. M. charantia can cause hypoglycemic coma and convulsions in children (12).
Especially in the last part of pregnancy, severe maternal hypoglycemia has been induced by quinine therapy. Recommendation. In pregnancy, quinine can be used for therapy of acute chloroquine-resistant falciparum malaria. The potential risk for the fetus due to the therapy is much less than the hazards due to the severe maternal disease. Attention should be paid to possible maternal hypoglycemia. Even though embryotoxic effects due to quinine in analgesic compounds are not to be expected, these agents should be avoided because they do not conform to good therapeutical practice.
Effects Chemically related to choline, ALC has many of the same effects. It acts as an anti-oxidant increases the levels of choline acetyl-transferase in the brain transports fats into the mitochondria, the part of the cell which creates energy enhances communication between the brain's hemispheres reduces triglyceride levels and removes ketones (fat waste products) from the blood helps control hypoglycemia alleviates angina attacks and has been used in the treatment of diabetes, infertility, liver disease, and kidney disease. It may help fight cancer by boosting the effect of lymphocytes, white blood cells that serve the immune system. It also slows down the cell damage caused by age-related conditions and may accelerate the repair of damaged DNA in cells ravaged by free radicals. It may help protect the brain from the effects of aging by preventing the accumulation of lipofuscin in the brain. Studies have shown that doses of anywhere from 2000 to 3500 mg a day can slow the onset of...
Severe cardiac dysrhythmias and major hypoglycemia have occurred in patients taking disopyramide with some macrolide antibiotics, especially erythromycin and clarithromycin (153). Symptomatic hypoglycemia developed in a 59-year-old man treated with a combination of disopyramide (50 mg day) and clarithromycin (600 mg day) (155).
In 561 patients with HbA1c of at least 8.0 on stable treatment with a sulfonylurea, piogli-tazone was added for 16 weeks in a doubleblind study (90C). The incidence of edema increased from 2 in the placebo group to 7 . There were more episodes of hypoglycemia, a dose-related increase in body weight, and a dose-related fall in hemoglobin with pioglita-zone. The frequency of adverse cardiovascular effects was the same.
The pharmacokinetics, pharmacodynamics, and clinical efficacy of repaglinide, and its role in the management of type 2 diabetes have recently been reviewed (72M). The overall incidence of hypoglycemia was similar to that reported with sulfonylureas, but the incidence of serious hypoglycemia was lower. Other adverse effects were respiratory tract infections and headache. Cardiovascular events and cardiovascular mortality were not different from those in users of sulfonylureas. In Europe repaglinide is contraindicated in patients with severe liver dysfunction and it is not recommended in people over 75 years old in America the advice is to use repaglinide cautiously in patients with impaired liver function and there is no restriction on its use in elderly patients. Metabolism Repaglinide has a short duration of action and improves postprandial hy-perglycemia, a potential risk factor for cardiovascular changes (74C). In a double-blind, multiple-dose, parallel-group study repaglinide...
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